Evaluated articles

eLife assessment

In this manuscript, the authors present a wealth of fMRI data at both 3T and 7T to identify a scene-selective region of the intraparietal gyrus ("PIGS") that appears to have some responsivity to characteristics of ego-motion. In a series of experiments, they delineate the anatomical location of PIGS and functionally differentiate it from nearby V6 and OPA. Evidence for these important findings is solid, but further investigations as to the role of this region in processing ego-motion will be needed to confirm this conclusion.

eLife Assessment

This study provides a valuable contribution to our understanding of causal inference in visual perception. The evidence provided through multiple well-designed psychophysical experiments is convincing. The current study targets very specific visual features of launch events, future work will be able to build on this to study the implementation of causal inference in general.

eLife assessment

Songbirds provide a tractable model system to study mechanisms of vocal production and sequencing, and past work showed that the lesions to LMAN, the output of a basal ganglia thalamocortical loop, reduced vocal variability, consistent with a role in motor exploration. In this fundamental work, the authors rigorously examined how lesions to an understudied neighboring region, MMAN, part of a parallel basal ganglia loop, affect singing in Bengalese finches, whose songs exhibit complex sequential transitions. The authors provide compelling evidence that MMAN lesions resulted in increased sequential variability but do not affect syllable acoustic structure, showing that distinct frontal systems can have distinct functions for producing and sequencing song syllables.

eLife Assessment

This important study provides evidence supporting the hypothesis that postnatal visual experience shapes the patterns of functional connectivity between extrastriate visual cortex and frontal regions, by comparing neonates, blind and sighted adults using resting-state fMRI. The evidence supporting the main claim is convincing, and the authors' interpretations are appropriately calibrated in the discussion. Nevertheless, the study design and methodology are inherently limited to resolve the underlying mechanisms driving connectivity changes during neurodevelopment (experience-related plasticity vs post-natal experience-independent maturation). This study will be of broad interest to neuroscientists and neuroimaging researchers studying vision, plasticity and brain development.

eLife assessment

This study provides direct evidence showing that Kv1.8 channels provide the basis for several potassium currents in the two types of sensory hair cells found in the mouse vestibular system. This is an important finding because the nature of the channels underpinning the unusual potassium conductance gK,L in type I hair cells has been under scrutiny for many years. The experimental evidence is compelling and the analysis is rigorous. The study will be of interest to cell and molecular biologists as well as vestibular and auditory neuroscientists.

eLife Assessment

This valuable study reports on the characteristics of premotor cortical population activity during the execution and observation of a moderately complex reaching and grasping task. By using new variants of well-established techniques to analyse neural population activity, the authors provide solid evidence that while the geometry of neural population activity changes between execution and observation, their dynamics are largely preserved. Although these findings are novel and robust, pending additional controls and analyses, the authors should further clarify the functional implications of their findings.

eLife assessment

This study provides a valuable theoretical exploration of non-enzymatic sustained replication of RNA systems, in the parabolic growth regime of the evolution of putative primordial replicators. It provides convincing evidence that parabolic growth mitigates the error threshold catastrophe, thus demonstrating another way in which this regime contributes to the maintenance of genetic diversity. The findings shed light on relevant evolutionary regimes of primordial replicators, with potential applicability to our understanding of the origin of life.

eLife assessment

This manuscript presents valuable findings on the identification of epigenetically mediated control for the recognition of dihydropyrimidine dehydrogenase (DPYD) gene expression that is linked with cancer treatment resistance using 5-fluorouracil. The evidence is compelling, supported by data from patient-derived specimens and direct assessment of 5-fluorouracil sensitivity, which provides confidence in the proposed mechanisms. The model is additionally supported by genome data from a population with high "compromised allele frequency". This work will interest those studying drug resistance in cancer therapy.

eLife assessment

This important study using engineered mouse models provides a first and compelling demonstration of a pathogenic phenotype associated with lack of expression of p53AS, an isoform of the p53 protein with a different C-terminus than canonical p53. The role of this isoform has been elusive so far and this first demonstration represents a substantial advance in our understanding of the complex role(s) of p53 isoforms. The revised manuscript adequately addresses previous concerns.

eLife assessment

This study offers valuable insight into the remarkable resistance of tardigrades to ionizing radiation by showing that radiation treatment induces a suite of DNA repair proteins and by identifying a strongly induced tardigrade-specific DNA-binding protein that can reduce the number of double-strand breaks in human U2OS cells. The evidence of upregulation of repair proteins is convincing, and the case for a role of the newly identified protein in repair can be strengthened as genetic tools for tardigrades become better developed. The results will interest the fields of DNA repair and radiobiology as well as tardigrade biologists.

eLife assessment

This study presents new data highlighting the importance of appropriate coenzyme A handling in the mitochondria for maintaining appropriate energy production capacity. Several findings regarding the role of a key metabolic enzyme in how skeletal muscle cells use different substrates for energy production are valuable and supported by solid evidence, but there are concerns whether the data support the conclusion that ACOT2 regulates mitochondrial matrix acyl-CoA levels in white skeletal muscle to facilitate fatty acid oxidation β-oxidation.

eLife assessment

This study characterizes the composition and immune diversity of the zebrafish kidney, the immune organ equivalent to human bone marrow, with convincing single-cell transcriptomic data of hematopoietic cells and immunocytes. The key findings suggest that zebrafish kidney is a secondary lymphatic organ, and that hematopoietic stem cells in zebrafish may exhibit trained immunity, which are the unique features of the fish immune system. This study provides new and valuable insights into the antiviral response in teleost fish, which will be of interest to biologists in general, and to immunologists and cancer researchers in particular.

eLife Assessment

This useful work provides insight into agonist binding to nicotinic acetylcholine receptors, which is the stimulus for channel activation that regulates muscle contraction at the neuromuscular junction. The authors use in silico methods to explore the transient conformational change from a low to high affinity agonist-bound conformation as occurs during channel opening, but for which structural information is lacking owing to its transient nature. The simulations indicating that ligands flip ~180 degrees in the binding site as it transitions from a low to high affinity bound conformation are solid. A limitation is the approximation of binding energies using Poisson-Boltzmann Surface Area and mismatch between calculated and experimental binding energies for two of the four ligands tested. Nonetheless, this work presents an intriguing picture for the nature of a transient conformational change at the agonist binding site correlated with channel opening.

eLife assessment

This important study presents the structure of human heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT) in the acetyl-CoA bound state, providing the first description of the architecture of this family of integral membrane enzymes, and revealing the mode of acetyl-CoA binding. The structural work is convincing, with a high resolution and isotropic single-particle cryoEM map and an atomic model that is well-justified by the density map, with strong density for the acetyl-CoA ligand. However, experimental support for the molecular mechanism of the HS acetylation reaction and the impact of disease-causing mutations is incomplete. This work will be of interest to biochemists and structural biologists studying the structure and function of integral membrane enzymes, as well as those interested in genetic diseases resulting from mutations in this family of enzymes, such as mucopolysaccharidosis IIIC (MPS III-C).

eLife assessment

This study presents fundamental findings that advance our understanding of the role of phenotypic aging in cancer risk. This article presents compelling results that show Phenotypic Age Acceleration (PhenoAgeAccel) can predict cancer incidence of different types and could be used with genetic risk to facilitate the identification of cancer-susceptible individuals. These results will be of broad interest to the research community and clinicians.

eLife assessment

This manuscript shows that manipulating the expression of the histone acetyltransferase Gcn5 affects blood cell homeostasis in the Drosophila larval hematopoietic organ. The data suggest a link between autophagy and the mTOR pathway, as could be expected from the literature. The authors use several genetic manipulations as well as some chemical modulators to generate solid evidence supporting most of their conclusions, but some of the analyses are inadequate and would benefit from improvement.

eLife Assessment

By leveraging optical coherence tomography this study provides important insight into the deformation of human fingertip ridges when contacting raised features such as edges and contours. The study provides compelling evidence that such features tend to cause deformation and relative movement of what the authors term ridge flanks rather than bending of the ridges themselves.

eLife assessment

This important study provides convincing evidence of artifactual calcium micro-waves during calcium imaging of populations of neurons in the hippocampus using methods that are common in the field. The work raises awareness of these artifacts so that any research labs planning to do calcium imaging in the hippocampus can avoid them by using alternative strategies that the authors propose.

eLife assessment

This important study presents the first comprehensive catalog of the large neurons that compute optic flow in any insect. The morphological reconstructions from volume electron microscopy of the large arbors of these neurons, the Lobula Plate Tangential Neurons, were followed by the examination of their spatial arrangement to estimate their individual receptive fields and predict their optimal motion sensitivity. This compelling, rigorous data set, which includes the synaptic connectivity of the neurons under study with major target neurons in the fly brain, establishes a foundation for future studies on visual processing on the basis of a known connectome plus genetic driver lines to manipulate its constituent neurons. It will be of interest beyond insect vision to those studying sensory processing and neural circuit function.

eLife assessment

Shore et al. report the important effects of a heterozygous mutation in the KCNT1 potassium channel on ion currents and firing behavior of excitatory and inhibitory neurons in the cortex of KCNT1-Y777H mice. The authors provide solid evidence of physiological differences between this heterozygous mutation and their previous work with homozygotes. The reviewers appreciated the inclusion of recordings in ex vivo slices and dissociated cortical neurons, as well as the additional evidence showing an increase in persistent sodium currents in parvalbumin-positive interneurons in heterozygotes.